Parkinson’s Disease And Drug Therapy Flashcards
Disturbance of planning?
Apraxia
Ballismus?
High amplitude flailing of the limbs on one side of the body
Hemiballismus pathophysiology?
Disruption of indirect pathway at STN
What causes hemiballismus?
Stroke
Tic disorder?
Brief repetitive stereotype movements with a premonitory urge (uncomfortable feeling)
Coprolalia?
Swearing
Chorea?
Jerky, brief, not repetitive, flowing contracting
Chorea pathophysiology?
problem in STN in indirect pathway
What causes chorea?
Huntington’s and neuroleptics
Huntington’s chorea genetics?
Trinucleotide repeat chromosome 4
Autosomal dominant
Longer the repeat sequence the earlier the disease presents
Myoclonus?
Brief movement, rapid onset and offset. Positive and negative
Causes of myoclonus
Prion
Juvenile myoclonus epilepsy
Brain hypoxia
Dystonia?
Abnormal twisting posture, may be associated with jerking movement
Possible pathophysiology for dystonia?
Abnormal dopaminergic activity in basal ganglia: blocking dopamine receptors and treatment with levodopa
Dystonia causes?
Huntington’s, Parkinson’s, encephalitis, stroke, brain injury
Kinetic tremor?
Nose finger
Essential tremors
Predominantly postural
Essential tremor is due to?
Gabaergic dysfunction in cerebellum
Problems with dopamine blocking agents?
Oculogyric crisis (spasmodic movements of eye usually upwards), neuroleptic malignant syndrome
Subacute: drug induced Parkinsonism
Long term: tardive dyskinesia
Parkinsonism triad of symptoms?
Bradykinesia, rigidity and shaking (resting tremor)
Parkinson’s: REM parasomnia?
Sleep disorders, unusual movement, emotion, behaviour and dreams between different stages of sleep
Pathophysiology of PD?
Lack of dopamine from substantia nigra
Percentage cell loss of dopaminergic cells of substantia nigra?
70%
Causes of Parkinsonism?
Idiopathic over 80, diffuse levy body, drugs, hydrocephalus, Wilson’s disease, rare familial, cerebri vascular disease
Break-down of levodopa?
Dopa decarboxylase
MAO inhibitors: type A and B:
A: serotonin, adrenaline, noradrenaline and dopamine
B: dopamine
We use B because selective e.g selegiline and rasagiline
COMT inhibitor?
Entacapone/tolcapone.
Makes dyskinesia worse, diarrhoea, liver disease
Dopamine agonists?
Work on dopamine receptors
Cons, Dopamine dysregulation syndrome
E.g apomorphine s/c infusion but skin nodules
Disturbance of coordination is called?
Ataxia
Example of tic disorders?
Simple- coughing blinking
Complex- twirling jumping
Plus motor disorder and coprolalia
How do you reduce tic disorder?
Distraction and concentration
What is the more sever expression of spectrum of tic disorders?
Tourette syndrome
Tic disorder causes?
Complex genetic inheritance Post infectious immune Often associate with other co-morbid conditions 50%- ADHD 33.3% - OCD And up to 50% with anxiety
What is the clinical presentation of Huntington’s?
Cognitive- inability to make decisions multitask and slowness of thought
Behavioural- irritability, depression apathy anxiety delusions
Physical- chorea, motor persistence dystonia and eye movements
What can myoclonus be treated by?
Antiepilieptics
What is th pathophysiology of tremor?
Increased activity in the cerebellothalamocortical circuit
PD is due to?
Dopamine dysfunction in the pallidus
Drugs to treat hyperkinetic movement disorders?
Dopamine receptor blocking agents
(eg haloperidol, chlorpromazine, pimozide, risperidone)
Dopamine depleting agents
(eg Tetrabenazine, Reserpine)
Atypical anti-psychotics
(eg Clozapine, Olanzapine, Aripiprazole)
Oculogyric crisis?
Very characteristic acute response to certain drugs Fixed stare, upward deviation of eyes Neck extension Trunk extension Jaw spasms +/- tongue protrusion ‘Acute dystonic’ reaction
Neuroleptic malignant syndrome?
Rigidity/ muscle breakdown – raised CPK.
●Fever
●Autonomic instability (volatile BP/PR)
●Confusion
Tardive dyskinesia?
Choreic oral-facial movements (video), dystonic trunk posturing
●Exact mechanism unclear – likely dopamine supersensitvity of basal ganglia –ie secondary receptor/ plastic changes
●Treatment -gradual withdrawal of offending agent, substitution with an atypical anti-psychotic ; use of a dopamine depleting agent (tetrabenazine); use of a benzodiazepine (clonazepam) if distressing
No motor symptoms of Parkinson’s?
Depression anxiety Dementia: slowed thoughts Postural hypotension, hypersalivation Restless legs rem parasomnia Reduced sense of smell
PD pathophysiology?
Decreased dopamine input leads to reduced activation of direct pathway and reduced inhibition of indirect pathway, leading to reduced movements
What else do you find in Parkinson’s?
Lewy bodies and intraneuronal protein inclusion
Early drug therapies for Parkinson’s?
Amantadine – Initially anti-flu agent
Glutamate agonist
Anti-cholinergics – Procyclidine, Benzhexol
May help with tremor
Limited by side effects
(confusion, urinary retention, dry mouth…)
Mono-amine oxidase inhibitors
Non drug therapies?
Not clear how it works (but it does!)
Probably high freq stimulation
causing ‘jamming’(inhibition of
neurons by depolarising block)
Also disrupts abnormally
synchronous basal ganglia rhythms
Favoured target subthalamic nucleus (STN) for PD Also pallidum (for dystonia) and thalamus (for tremor)
Disease will still progress and no effect on non-motor -dementia, -dysautonomia, -postural instability…..
- Future – neurorestorative (stem cells)
- Neuroprotective (growth factors)
